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Parkinson's disease‐related DJ ‐1 modulates the expression of uncoupling protein 4 against oxidative stress
Author(s) -
Xu Shaoqing,
Yang Xiaodong,
Qian Yiwei,
Xiao Qin
Publication year - 2018
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14297
Subject(s) - oxidative stress , gene knockdown , viability assay , oxidative phosphorylation , mitochondrion , microbiology and biotechnology , western blot , knockout mouse , chemistry , reactive oxygen species , biology , biochemistry , cell , apoptosis , gene
Loss of function mutations of DJ ‐1 ( PARK 7 ) have been linked to the pathogenesis of Parkinson's disease. Antioxidative stress is one of the multi‐protective functions of DJ ‐1, and oxidation of cysteine 106 has been proposed to regulate the protective activity of DJ ‐1. Uncoupling protein 4 ( UCP 4) is located in the inner membrane of mitochondria and functions to protect against oxidative stress. In this study, we used neuronal ( SH ‐ SY 5Y) cells and DJ ‐1 knockout mice to elucidate whether DJ ‐1 regulated oxidative stress via modulating the expression of UCP 4, and the underlying mechanism. The downstream products of oxidative stress, mitochondrial membrane potential (ΔΨm) and cell viability were also investigated. We found that UCP 4 was up‐regulated upon 1‐methyl‐4‐phenylpyridinium ( MPP + ) stimulation in SH ‐ SY 5Y cells, which was enhanced by wild type DJ ‐1 and alleviated by DJ ‐1 knockdown. Expression of UCP 4 in DJ ‐1 knockout mice was lower compared with wild‐type mice. In addition, up‐regulation of UCP 4 was alleviated by inhibition of oxidized DJ ‐1, and enhanced by increase in oxidized DJ ‐1 under conditions of oxidative stress using western blot analysis. Moreover, over‐expression of UCP 4 in DJ ‐1 knockdown cells partially reversed the decrease in cell viability, ΔΨm, as well as the increase in products of oxidative stress upon MPP + stimulation. Furthermore analysis showed that DJ ‐1 regulated transcriptional activity of UCP 4 partially via Nuclear factor‐kappa B ( NF ‐ κB ) pathway in the presence of MPP + . Together, our results suggested DJ ‐1 might regulate the expression of UCP 4 by oxidation of DJ ‐1 and partially via NF ‐ κB pathway in its protective response to oxidative stress.